Studies on protein phosphorylation in intact rabbit kidney tubules will include: (a) An examination of endogenous protein phosphorylation in cortical, medullary, and papillary tubules. This will be performed by 33Pi labeling of the phosphate pool of the renal cells followed by polyacrylamide gel electrophoresis to separate proteins. (b) An examination of the effects of parathyroid hormone and antidiuretic hormone on endogenous protein phosphorylation. Microdissected segments from proximal convoluted tubules and collecting ducts will be utilized to determine physiologically significant protein substrates. Relationships will be sought between protein phosphorylation and (i) antidiuretic hormone and microtubular proteins, or (ii) parathyroid hormone and gluconeogenesis. Studies in the isolated perfused rat kidney will correlate protein phosphorylation with the effects of parathyroid hormone on ion transport and gluconeogenesis. Studies in rabbit kidney tubule homogenates and subcellular fractions will include: (a) measurement of protein kinase and protein phosphatase activity and their modulation by cyclic AMP and other agents. (b) Determination of the pattern of protein phosphorylation by localization of endogenous kinases, phosphatases, and substrates. Studies in cultured pig kidney cells, LLC-PK1, will include a description and distribution of cyclic AMP-dependent protein kinase. Cultured giant cell tumors of human bone will be used as a model to study PTH action.